PROJECT SUMMARY Serious bacterial infections including infective endocarditis and skin and soft tissue infections are among the most common medical complications in persons who inject drugs (PWID). Hospitalizations for injection-related infective endocarditis increased twelve-fold between 2010 and 2015 and for heroin-related skin and soft tissue infections doubled over the last two decades. Costs of these diseases have also increased dramatically. While there are ongoing hospital-based programs to reduce injection-related bacterial infections, their long-term effectiveness, costs, and cost-effectiveness are unknown. Longitudinal investigation of these interventions is urgently needed to improve outcomes given the rapid expansion of the US opioid epidemic, but is challenging due to the relapsing nature of OUD, the heterogeneous nature of persons who inject opioids, and the shifting nature of the drug supply. Simulation modeling can augment evidence from trials by projecting the clinical and economic outcomes over longer time horizons for different populations. This proposed research will use simulation modeling to examine the impact of changes in injection opioid use practices as well as hospital-based interventions aimed at addressing the underlying OUD on the incidence of injection-related bacterial infections with the following scientific aims: Aim 1: To develop a simulation model of injection opioid use to project long-term incidence, outcomes, and costs of injection-related infective endocarditis, skin and soft tissue infections, and overdose. Aim 2: To estimate the clinical impact, costs, and cost-effectiveness of hospital-initiated addiction care and rapid-access linkage to post-hospital medication treatment for persons who inject opioids. Aim 3: To perform a comprehensive economic evaluation alongside an ongoing clinical trial and to use the simulation model to estimate the long-term clinical effectiveness of a hospital-based skin and needle hygiene program aimed to prevent bacterial infections among persons who inject opioids. During the K01 project period, the candidate will develop a specific skill set in three primary domains: (1) advanced quantitative methods for simulation modeling; (2) understanding the design, operationalization, and evaluation of hospital-based interventions for PWID; and (3) measuring healthcare utilization and cost- effectiveness analyses alongside clinical trials. Training will be accomplished through an intensive combination of formal structured courses, training workshops and field experiences, applied research experience, and focused mentorship in mathematical modeling, biostatistics, addiction, hospital-based interventions, and health economics. Acquisition of these skills will allow the candidate to accomplish his long-term goal, which is to become an independently-funded investigator and global expert on clinical decision making and health policy at the intersection of substance use and infectious diseases.